Immunogenetics of Henoch–schoenlein Disease

Abstract

In order to investigate the genetic basis of susceptibility to Henoch-Schoenlein purpura (HS), blood samples of 152 patients, 105 of whom had renal disease, were collected in a two-step study. The evaluation of DRB, DQB and DQA polymorphism was done by analysis of the restriction polymorphisms produced by TaqI enzyme. DRB1*07 was less frequent in patients than in the control group (gene frequency 0.09 and 0.18, respectively; P = 0.0023), whereas 64% of the patients were positive for DRB1*01 and/or DRB1*11 compared with 48% of the control group (P = 0.0069). Polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) typing of DRB1*01- and DRB1*11-positive individuals did not show any deviation of frequencies of DRB1*01 subtypes between patients and controls, whereas among DRB1*11 subtypes DRB1*1104 was significantly increased in the patients (Pc = 0.033). The comparison between patients with renal disease and those without renal disease showed no significant differences in the frequency of the single DRB, DQB and DQA alleles. The study of restriction polymorphisms in the switch region of the constant genes alpha 1, alpha 2 and mu of the heavy chains of immunoglobulins, using the enzyme Sacl and a specific probe, did not show any difference between 44 patients and 54 controls. This study demonstrates that susceptibility to HS also has a genetic origin: on one hand, the presence of DRB1*01 or DRB1*11 makes disease onset easier; on the other hand, DRB1*07 could induce some resistance to the disease. It is suggested that, as well as for other diseases caused by an impaired immune response, single amino acids in a key position in the HLA-DRB molecule make it more or less easy to recognize some antigenic peptide, towards which an immune response leading to disease is triggered.

Henoch–Schönlein purpura

“…Studies from Spain, Italy and Turkey reported that HLA-DRB1Ã01, HLA-DRB1Ã11 and HLA-DRB1Ã14 alleles were associated with susceptibility to HSP [5][6][7]. A recent study from Turkey showed that HLA-B35 allele was associated with increased risk of HSP [8].…”

Interleukin 8 gene 2767 A/G polymorphism is associated with increased risk of nephritis in children with Henoch–Schönlein purpura

“…Different information has been reached in parallel to the developments in the science of immunology related to the pathogenesis of HSP, which is a leukocytoclastic small vessel vasculitis. Many studies were performed in the light of this information, and different results were stated [20][21][22][23][24][25][26][27][28][29][30][31].…”

CTLA-4 +49 A/G genotype and HLA-DRB1 polymorphisms in Turkish patients with Henoch–Schönlein purpura

“…The implication of HLA class II genes in the susceptibility to HSP has previously been described [10][11][12][13][14]. Although multiple genetic and environmental factors are considered to be involved in the pathogenesis of HSP, factors other than HLA remain to be determined.…”

“…Susceptibility to HSP has been observed in Italian and Spanish patients who carried human leukocyte antigen (HLA)-DRB1*01 and DRB1*11. Some evidence suggests that the disease is multifactorial, with both environmental and genetic factors contributing to its pathogenesis [10][11][12][13][14].…”